title: PEI-g-PEG-RGD/small interference RNA polyplex-mediated silencing of vascular endothelial growth factor receptor and its potential as an anti-angiogenic tumor therapeutic strategy.
abstract: Tumor angiogenesis appears to be achieved by the expression of vascular endothelial growth factor (VEGF) within solid tumors that stimulate host vascular endothelial cell mitogenesis and possibly chemotaxis. VEGF's angiogenic actions are mediated through its high-affinity binding to 2 endothelium-specific receptor tyrosine kinase, Flt-1 (VEGFR1), and Flk-1/KDR (VEGFR2). RNA interference-mediated knockdown of protein expression at the messenger RNA level provides a new therapeutic strategy to overcome various diseases. To achieve high efficacy in RNA interference-mediated therapy, it is critical to develop an efficient delivering system to deliver small interference RNA (siRNA) into tissues or cells site-specifically. We previously reported an angiogenic endothelial cell-targeted polymeric gene carrier, PEI-g-PEG-RGD. This targeted carrier was developed by the conjugation of the ανβ3/ανβ5 integrin-binding RGD peptide (ACDCRGDCFC) to the cationic polymer, branched polyethylenimine, with a hydrophilic polyethylene glycol (PEG) spacer. In this study, we used PEI-g-PEG-RGD to deliver siRNA against VEGFR1 into tumor site. The physicochemical properties of PEI-g-PEG-RGD/siRNA complexes was evaluated. Further, tumor growth profile was also investigated after systemic administration of PEI-g-PEG-RGD/siRNA complexes.
authors.affiliation: Department of Chemistry, BK School of Molecular Science, Polymer Research Institute, Pohang University of Science and Technology , Pohang, Korea.
authors.forename: Jihoon
authors.initials: J
authors.lastname: Kim
authors.forename: Sung Wan
authors.initials: SW
authors.lastname: Kim
authors.forename: Won Jong
authors.initials: WJ
authors.lastname: Kim
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D055785:Gene Knockdown Techniques / Q000379:methods; D018014:Gene Transfer Techniques / Q000295:instrumentation; D015316:Genetic Therapy / Q000295:instrumentation; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D010456:Peptides, Cyclic / Q000008:administration & dosage* / Q000138:chemical synthesis; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000138:chemical synthesis; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000032:analysis; D014162:Transfection / Q000379:methods; D014183:Transplantation, Heterologous / Q000379:methods; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000187:drug effects* / Q000378:metabolism*
chemical_list: C507107:PEI-g-PEG-RGD; D010456:Peptides, Cyclic; D034741:RNA, Small Interfering; D011092:Polyethylene Glycols; D040281:Vascular Endothelial Growth Factor Receptor-1